Molecular tweezers for hydrogen: Synthesis, characterization, and reactivity

Article abstract of DOI:10.1021/ja806627s

The first ansa-aminoborane N-TMPN-CH₂C₆H₄B(C₆F₅)₂ (where TMPNH is 2,2,6,6-tetramethylpiperidinyl) which is able to reversibly activate H₂ through an intramolecular mechanism is synthesized. This new substance makes use of the concept of molecular tweezers where the active N and B centers are located close to each other so that one H₂ molecule can fit in this void and be activated. Because of the fixed geometry of this ansa-ammonium-borate it forms a short N-H...H-B dihydrogen bond of 1.78 A as determined by X-ray analysis. Therefore, the bound hydrogen can be released above 100 °C. In addition, the short H...H contact and the N-H...H (154°) and B-H...H (125°) angles show that the dihydrogen interaction in N-TMPNH-CH₂C₆H₄BH(C₆F₅)₂ is partially covalent in nature. As a basis for discussing the mechanism, quantum chemical calculations are performed and it is found that the energy needed for splitting H₂ can arise from the Coulomb attraction between the resulting ionic fragments, or "Coulomb pays for Heitler-London". The air- and moisture-stable N-TMPNH-CH₂C₆H₄BH(C₆F₅)₂ is employed in the catalytic reduction of nonsterically demanding imines and enamines under mild conditions (110 °C and 2 atm of H₂) to give the corresponding amines in high yields. Copyright

Full text of DOI:10.1021/ja806627s

Published on Web 10/01/2008
Molecular Tweezers for Hydrogen: Synthesis, Characterization, and Reactivity
Victor Sumerin,† Felix Schulz,‡ Michiko Atsumi,† Cong Wang,† Martin Nieger,† Markku Leskela¨,†
Timo Repo,*,† Pekka Pyykko¨,† and Bernhard Rieger*,‡
Department of Chemistry, UniVersity of Helsinki, P.O. Box 55, FIN-00014 Helsinki, Finland, and
WACKER-Lehrstuhl fu¨r Makromolekulare Chemie, Technische UniVersita¨t Mu¨nchen, Lichtenbergstrasse 4,
D-85747 Garching bei Mu¨nchen, Germany
Received August 26, 2008; E-mail: timo.repo@helsinki.fi; rieger@tum.de
Scheme 1. Synthesis of Compound 1a
Amine formation is a fundamental reaction in chemical synthe-
sis.1 The importance of amines and their derivatives such as amides
and sulfamides in food, agrochemical, and pharmaceutical industries
is well recognized.2,3 Although countless methods are known for
the synthesis of amines, preparations under mild conditions, without
generation of waste, and without the use of transition-metals is a
a Reagents and conditions: (a) acetone, 95 °C, 48 h, 1.1 equiv K2CO3,
0.1 equiv KI, 1 equiv TMPNH; (b) -70 °C, Et2O, 2 equiv t-BuLi; (c) -20
to 20 °C, 12 h, (C6F5)2BCl.
challenging goal.4 Among the various methods, the widely used
transition-metal-catalyzed reductions of imines, enamines, and
nitriles are probably the most important.5 Unfortunately, transition-
metal catalysts are not only expensive, but their complete removal
from the reaction product is generally required in the production
of pharmaceutical intermediates due to toxicity concerns.6 Alter-
natively, main-group hydride reagents such as NaBH4 and LiAlH4
afford stoichiometric reductions, but involve tedious procedures and
produce toxic chemical waste.7 Metal-free reductions of imines by
organocatalysts, in combination with Hantzsch ester as the hydrogen
source, are known.8 Recently, several atom-economical transition-
metal-free methods such as Lewis acid-catalyzed amination,9
hydrosilation,10 and intermolecular hydroamination11 were reported.
More recently, the first nonmetal system which is able to reversibly
activate H2 was shown in pioneering studies by Stephan and co-
workers to be an effective catalyst for the hydrogenation of bulky
imines.12-14 Herein we report the metal-free catalytic hydrogenation
of nonsterically demanding imines and enamines.
Scheme 2. Reversible H2 Activation by System 1,2
65.48 ppm indicative of three-coordinate boron (Scheme 1).
Moreover, the difference in the chemical shifts ∆δp,m ) 13.61 ppm
of the F atoms in the para and meta positions of the C6F5 fragments
refers to a neutral boron center.10
Compound 1 reacted rapidly with H2 in toluene solution at 20
°C to give a white suspension of 2 in quantitative yield (Scheme
2). The NMR spectroscopic data exhibited a 11B NMR signal at
Understanding the actual mechanism of splitting and liberating
H2 by nonmetals and the nature of dihydrogen bond interaction in
these compounds is essential for learning how to design metal-
free systems for H2 storage and new hydrogenation catalysts.15-17
Although the liberation of H2 is expected to be thermodynamically
uphill, it is envisioned that if the energetic cost is small enough,
facile hydrogen liberation can take place.
1
-20.39 ppm (doublet, JBH ) 77 Hz) and the difference in the
chemical shifts of the F atoms (∆δp,m ) 3.68 ppm) indicated an
anionic four-coordinate borate.10 The H NMR spectrum showed
1
quartet and a broad singlet resonances at 3.91 ppm (B-H, 1JBH
)
74 Hz) and 7.55 ppm (N-H), respectively. The observation that
the methyl groups in catalyst 2 occur as two singlets (1:1 ratio)
accounts for a significant barrier of rotation around the N-benzyl
bond. Furthermore, the NMR data revealed that the conversion to
2 was completed in less than 5 min. An X-ray crystallographic
study of 2 (Figure 1) showed that the N-H· · ·H-B dihydrogen
bond (DHB) is rather short (1.78 Å).21,22 Thus, the air- and
moisture-stable catalyst 2 has been prepared on a gram scale (up
to 5 g) by an efficient three-step synthesis from readily available
precursors (Schemes 1, 2).
Interestingly, when a toluene solution of 2 (0.1M) was refluxed
at 110 °C in a closed system under reduced pressure, or a flow of
argon for 3 h, a 50% conversion of 2 to the bright yellow starting
compound 1 was observed. Continuing the reaction up to 20 h
resulted in the quantitative recovery of product 1. These findings
are in contrast to the nonbridged systems where the bound hydrogen
cannot be released thermally after activation.18
We recently reported the hydrogen activation by 2,2,6,6-
tetramethylpiperidine (TMPNH) in combination with B(C6F5)3.18
Whereas this reaction leads to the stable hydrogenated ionic product
[TMPNH2]+[BH(C6F5)3]-, an extraordinary intermediate with a
strong N-H· · ·H-B dihydrogen bond between the cation and the
anion was detected by nuclear magnetic resonance (NMR) spec-
troscopy. This observation prompted us to investigate a similar
intramolecular system for H2 activation where active B and N
centers are located close to each other.19 In this respect we designed
the ansa-compound N-TMPN-CH2C6H4B(C6F5)2 1 and developed
an effective procedure for the synthesis of a dehydrogenated product
1 starting from 2-bromobenzylbromide, 2,2,6,6-tetramethylpiperi-
dine and (C6F5)2BCl.20
The bright yellow oil 1 was isolated in total yield of 55% and
exhibited a single boron resonance in the 11B NMR spectrum at
To gain further insight into the mechanism of these reactions
and the nature of the N-H· · ·H-B dihydrogen-bond interaction,
we studied theoretically the structure, reaction path, and energetics.
† University of Helsinki.
‡ Technische Universita¨t Mu¨nchen.
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2008 American Chemical Society
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C O M M U N I C A T I O N S
Table 1. Catalytic Hydrogenation of Imines and Enamines by the
Nonmetal Compound 2: Catalyst 2 (0.01 mmol, 4%), Substrate
(0.25 mmol), and Toluene (0.7 mL) Were Refluxed (110°C) under
2 atm of H2 Pressure
Figure 1. Experimental X-ray structure of 2 (solvent molecules are omitted
for clarity).
the reaction pathway and describes an essentially direct route from
system 1 and H2 to catalyst 2.
The optimized structure of 2 is consistent with the X-ray data in
that the NH and BH bonds are oriented toward each other. The
calculated H · · ·H distance of 1.51 Å indicates the presence of a
strong partially covalent dihydrogen bond.23 That it is shorter than
the apparent experimental value of 1.78 Å, may largely be due to
the tendency of the X-ray technique to yield too short X-H bonds,
compared to neutron technique.21,30,31 Furthermore, not only the
short H · · ·H contact, but also the experimental topological param-
eters such as the N-H· · ·H (154°) and B-H· · ·H (125°) angles
show that the dihydrogen bond interaction in 2 is partially covalent
in nature.
For 2, the calculated B · · ·N distance R(B-N) ) 3.32 Å, where
R is the distance between two opposite unit charges, is close to the
obtained experimental data (3.36 Å). Then the Coulomb attraction
becomes -1/R ) -0.16 atomic units ) -413 kJ/mol. This is
comparable with the amount of energy required for the heterolytic
cleavage of the H-H bond, 432 kJ/mol.32 According to this
calculation the Coulomb attraction between the entire cation and
the entire anion can pay for the loss of the strong Heitler-London
covalent bond of H2, or “Coulomb pays for Heitler-London”.33
The two hydrogen atoms in system 2 (NH, BH) can be reunited
and thermally released due to the constraint geometry of this ansa-
ammoniumborate.20
To continue our experimental investigation, we examined the
reduction of imines with catalyst 2. Previous nonmetal systems have
shown stoichiometric reductions of the imine substrate
PhCH2NdCPh(H), because the resulting dibenzylamine inhibits the
active boron center because of adduct formation.13,34,35 At the
outset, when a toluene solution of catalyst 2 (4 mol percent) with
the imine from benzaldehyde and benzylamine was refluxed under
2 atm of H2 for 24 h, a 51% conversion of imine to amine was
observed. Continuing the reaction for up to 48 h gave 60%
conversion. To increase the yield, we heated the starting imine with
8 mol percent of catalyst 2 under the same H2 pressure (2 atm) in
toluene for 12 h. This setup resulted in the formation of dibenzy-
lamine in 99% yield (Table 1, entry 1). Moreover, a stoichiometric
Figure 2. Energies (kJ/mol) of the hydrogen activation reaction by 1
calculated at the PBE/6-31G(d) level of theory: black color, gas phase; blue
color, solution in benzene.
Until now, a broad spectrum of DHB interactions, including medium
(1.2-1.7 Å) and short (0.8-1.2 Å) distances, were discussed only
from a theoretical point of view.23 Furthermore, in earlier studies
of dihydrogen bonds, the partial charges A-Hδ+ · · · B-Hδ- were
often emphasized.24
Both
compound
2
and
the
simplified
system
[NH4]+[HB(CH3)2(CH2F)]- (2a) were considered.25,26 The reaction
path found (Figure 2) is similar to the reported concerted Lewis
acid-Lewis base (LA-LB) mechanisms for the hydrogen splitting
by similar phosphine-borane systems.27,28
The structure of the starting compound 1 was identified as a
minimum on the PBE potential energy surface. This ansa-
aminoborane makes use of the concept of molecular tweezers for
hydrogen. Owing to the constraint geometry and C-H· · ·F-C
interactions, which are common for this class of substances,29 the
boron and nitrogen atoms are oriented toward and in close but
noncoordinative contact to each other (a B-N distance of 3.43 Å
was detected). A hydrogen molecule can easily fit into this void
and may interact with both active centers of the amine-borane pair.
An early transition state (TS) with a short H-H distance of 0.78
Å has been located and represents the highest stationary point on
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C O M M U N I C A T I O N S
Scheme 3. Proposed Mechanism for the Catalytic Hydrogenation
of Imines by 2
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formation (3), and hence the sensitivity to steric factors at the R
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intramolecular mechanism. The structural and theoretical findings
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Acknowledgment. Supported was provided by the DAAD (D/
05/51658), Academy of Finland (123248), the Finnish CoE of
Computational Molecular Science, Magnus Ehrnrooth Foundation
(C.W.), Academy of Finland, and JSPS (M.A.). CSC, Espoo
provided computing resources. The authors are very grateful to Dr.
S. Heikkinen for help with NMR.
(33) More quantitative estimates for the simplified system 2a showed that the
cation and anion charge centers are located very close to the N and B atoms,
respectively. In a Morokuma energy decomposition for 2a, the ionic
(electrostatic), Pauli repulsion, and orbital interaction energies were-474,
+167, and-176 kJ/mol, respectively. An issue is the possibility of curve
crossing between ionic and covalent states of the loaded complexes at large
R. However for 2a, the vertical ionization potential (borate) is bigger than
the electron affinity (ammonium) and hence there is no such crossing. The
ionic ground-state of the type [NH4]+[HB(CH3)2(CH2F)]- prevails when
R approaches infinity.
(34) Chase, P. A.; Jurca, T.; Stephan, D. W. Chem. Commun. 2008, 1701–1703.
(35) Chen, D.; Klankermayer, J. Chem. Commun. 2008, 2130–2131.
(36) Previous nonmetal systems have shown stoichiometric reductions of the
imine substrates p-R-C6H4CH2NdCPh(CH3) and CH3NdCPh(CH3) (Table
1, entries 2, 3, 6, 7).
Supporting Information Available: Experimental procedures,
characterization data of all new compounds, copies of NMR spectra,
and X-ray crystallography data of 2. This material is available free of
charge via the Internet at http://pubs.acs.org. Structure parameters for
compound 2 are also available free of charge from Cambridge
Crystallographic Data Centre under reference number CCDC-694515.
JA806627S
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